The proliferative potential of normal mammalian somatic cells is limited, with the vast majority daughter cells eventually entering either a senescent state or undergoing apoptotic crisis. In rodent cell cultures, the emergence of immortalized cell lineages also occurs at a readily detectable frequency. To evaluate the roles of gene products that modulate higher order chromatin structure in these growth regulatory processes, chromodomain-containing HP1 family proteins, previously linked to heterochromatin-mediated silencing, have been examined. Proteins of this class, specifically M31, M32, and HP1-alpha, were demonstrated to extend proliferative potential and protect against crisis. No significant increase in immortalization was observed. Such findings suggest a direct link between senescence and the integrity of higher- order chromatin-mediated silencing. - senescence, aging, cancer, epigenetic inheritance, chromatin, heterochromatin